Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation ...of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo.
Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment.
Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle.
Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2.
Background
In recent years, Copper-64 (T
1/2
= 12.7 h) in the chemical form of copper dichloride (
64
CuCuCl
2
) has been identified as a potential agent for PET imaging and radionuclide therapy ...targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of
64
CuCuCl
2
, using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model.
Results
The highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively.
Conclusions
To the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of
64
CuCuCl
2
in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.
The High-Altitude Water Cherenkov (HAWC) Observatory is sensitive to gamma rays and charged cosmic rays at TeV energies. The detector is still under construction, but data acquisition with the ...partially deployed detector started in 2013. An analysis of the cosmic-ray arrival direction distribution based on 4.9 x 10 super(10) events recorded between 2013 June and 2014 February shows anisotropy at the 10 super(-4) level on angular scales of about 10degrees. The HAWC cosmic-ray sky map exhibits three regions of significantly enhanced cosmic-ray flux; two of these regions were first reported by the Milagro experiment. A third region coincides with an excess recently reported by the ARGO-YBJ experiment. An angular power spectrum analysis of the sky shows that all terms up to l = 15 contribute significantly to the excesses.
► SBA-16 substrate modified with 1wt.% of P is an efficient support for NiMoW HDS catalysts. ► The NiMoW/SBA-16 sulfide catalyst with 1wt.% of P is more active in HDS reaction than the P-free ...counterpart. ► The formation of “onion-type” Mo(W)S2 structure is detrimental for HDS activity.
P-containing SBA-16 mesoporous systems were used as supports of ternary Ni–Mo–W hydrodesulfurization (HDS) catalysts. The samples were characterized by a variety of techniques (N2 adsorption–desorption isotherms, XRD, TPR, TPD-NH3, DRS UV–vis and HRTEM). XRD profiles evidenced the formation of crystalline Mo1-xWxO3 and NiMoO4 phases on the surface of oxide catalyst precursors with high P-loadings (1.0 and 1.6wt.%). The UV–vis DRS measurements showed a substantial decrease of energy band gap after P-loading onto the SBA-16 substrate with respect to P-free sample. The sulfided catalysts were tested in separate HDS of dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT) reactions performed in a batch reactor at 320°C and H2 pressure of 5.0MPa. For both HDS reactions, the initial catalyst activity displayed a volcano-type curve indicating that catalyst behavior depends strongly on the phosphorous loading being all catalysts more active in the HDS of DBT then in the HDS of 4,6-DMDBT. The NiMoW/SBA-16 catalyst loaded with optimized amount of phosphorous (1.0wt.%) showed superior initial activity than the P-free counterpart. This effect was attributed to the enhancement of active phases dispersion on the support surface, as revealed by HRTEM measurements. It was found that the formation of “onion-type” Mo(W)S2 phases on the catalyst surface was detrimental for the HDS activity. At reaction time of 5h, the most active NiMoW/SBA-16 catalyst loaded with 1.0wt.% of P showed similar activity in both HDS of DBT and 4,6-DMDBT reactions. It was found that HYD route of both reactions was promoted by the support modification with P and due to inhibition of coordinatively unsaturated sites (CUSs) by competitive adsorption of products (mainly H2S).
Aims: Research into the relationship between pathogens, faecal indicator microbes and environmental factors in beach sand has been limited, yet vital to the understanding of the microbial ...relationship between sand and the water column and to the improvement of criteria for better human health protection at beaches. The objectives of this study were to evaluate the presence and distribution of pathogens in various zones of beach sand (subtidal, intertidal and supratidal) and to assess their relationship with environmental parameters and indicator microbes at a non-point source subtropical marine beach. Methods and Results: In this exploratory study in subtropical Miami (Florida, USA), beach sand samples were collected and analysed over the course of 6 days for several pathogens, microbial source tracking markers and indicator microbes. An inverse correlation between moisture content and most indicator microbes was found. Significant associations were identified between some indicator microbes and pathogens (such as nematode larvae and yeasts in the genus Candida), which are from classes of microbes that are rarely evaluated in the context of recreational beach use. Conclusions: Results indicate that indicator microbes may predict the presence of some of the pathogens, in particular helminthes, yeasts and the bacterial pathogen Staphylococcus aureus including methicillin-resistant forms. Indicator microbes may thus be useful for monitoring beach sand and water quality at non-point source beaches. Significance and Impact of the Study: The presence of both indicator microbes and pathogens in beach sand provides one possible explanation for human health effects reported at non-point sources beaches.
To cite this article: Huerta‐Yepez S, Baay‐Guzman GJ, Bebenek IG, Hernandez‐Pando R, Vega MI, Chi L, Riedl M, Diaz‐Sanchez D, Kleerup E, Tashkin DP, Gonzalez FJ, Bonavida B, Zeidler M, Hankinson O. ...Hypoxia Inducible Factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis. Allergy 2011; 66: 909–918.
Background: New therapies are necessary to address inadequate asthma control in many patients. This study sets out to investigate whether hypoxia‐inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment.
Methods: Mice conditionally knocked out for HIF‐1β were examined for their ability to mount an allergic inflammatory response in the lung after intratracheal exposure to ovalbumin. The effects of treating wild‐type mice with either ethyl‐3,4‐dihydroxybenzoate (EDHB) or 2‐methoxyestradiol (2ME), which upregulate and downregulate HIF, respectively, were determined. HIF‐1α levels were also measured in endobronchial biopsies and bronchial fluid of patients with asthma and nasal fluid of patients with rhinitis after challenge.
Results: Deletion of HIF‐1β resulted in diminished AAI and diminished production of ovalbumin‐specific IgE and IgG1. EDHB enhanced the inflammatory response, which was muted upon simultaneous inhibition of vascular endothelial growth factor (VEGF). EDHB and 2ME antagonized each other with regard to their effects on airway inflammation and mucus production. The levels of HIF‐1α and VEGF increased in lung tissue and bronchial fluid of patients with asthma and in the nasal fluid of patients with rhinitis after challenge.
Conclusions: Our results support the notion that HIF is directly involved in the development of AAI. Most importantly, we demonstrate for the first time that HIF‐1α is increased after challenge in patients with asthma and rhinitis. Therefore, we propose that HIF may be a potential therapeutic target for asthma and possibly for other inflammatory diseases.
The first limits on the prompt emission from the long gamma-ray burst (GRB) 130427A in the >100 GeV energy band are reported. GRB 130427A was the most powerful burst ever detected with a redshift z ≲ ...0.5 and featured the longest lasting emission above 100 MeV. The energy spectrum extends at least up to 95 GeV, clearly in the range observable by the High Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory, a new extensive air shower detector currently under construction in central Mexico. The burst occurred under unfavorable observation conditions, low in the sky and when HAWC was running 10% of the final detector. Based on the observed light curve at MeV-GeV energies, eight different time periods have been searched for prompt and delayed emission from this GRB. In all cases, no statistically significant excess of counts has been found and upper limits have been placed. It is shown that a similar GRB close to zenith would be easily detected by the full HAWC detector, which will be completed soon. The detection rate of the full HAWC detector may be as high as one to two GRBs per year. A detection could provide important information regarding the high energy processes at work and the observation of a possible cut-off beyond the Fermi Large Area Telescope energy range could be the signature of gamma-ray absorption, either in the GRB or along the line of sight due to the extragalactic background light.
Structural, morphological and compositional characterizations of zinc selenide nanoparticles (NPs-ZnSe) are discussed in this work. NPs-ZnSe were obtained by colloidal synthesis in aqueous solution ...at room temperature, atmospheric pressure and without inert atmosphere. The synthesis was carried out using zinc chloride (ZnCl2) and elemental selenium as precursors. A mix of Na5P3O10 and NaOH called Extran was used as surfactant. Molar concentration and pH of the aqueous solution were varied to study their effect on the crystalline properties of the nanoparticles. The XRD measurements show that the NPs-ZnSe exhibits a cubic phase structure. The size of the nanocrystals was between 3nm and 4.7nm. HRTEM analysis showed that NPs-ZnSe exhibit semi-spherical shape. The presence of zinc and selenium in the NPs-ZnSe was confirmed through EDS measurements.
•ZnSe nanoparticles were obtained by colloidal synthesis at room temperature.•XRD measurements showed that the nanoparticles exhibit a cubic phase structure.•The size of the nanocrystals was founded between 3nm and 4.7nm.•HRTEM analysis showed that ZnSe nanoparticles exhibit semi-spherical shapes.
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